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Human T-Cell Biology in a Mouse Environment

  • Nicolas Legrand
  • Hergen Spits
Chapter

Abstract

After decades of incremental optimization efforts, mouse models of human hematopoiesis supporting de novo human hematopoietic cell development in situ have been obtained. Although these new humanized mouse models represent a major achievement, they still exhibit several limitations and do not fully support optimal human leukocyte biology. Still, they provide clues on what could be the milestones to target for the next generation of humanized mouse models of the immune system, especially when dealing with the functionality of the human hematopoietic cells in such a setting. In this chapter, we specifically address human T-cell development and homeostasis in a selection of recent human immune system (HIS) mouse models, discuss their intrinsic limitations for prospective study of human T-cell biology, and speculate on future areas of HIS mouse model improvement.

Keywords

Humanized mouse models Human immune system mice BRG BRGS NSG NOG BLT Human hematopoiesis Hematopoietic stem and progenitor cell transplantation T lymphocytes 

Abbreviations

BLT

Bone marrow, liver, thymus

BRG

BALB/c Rag2−/− IL-2Rγc −/−

BRGS

BALB/c Rag2−/− IL-2Rγc −/− SIRPαNOD

DC

Dendritic cells

FDC

Follicular dendritic cells

FL

Fetal liver

FRC

Fibroblastic reticular cells

GvHD

Graft-versus-host disease

HIS

Human immune system

hHSPC

Human hematopoietic stem and progenitor cells

hTSPC

Human thymus seeding progenitor cells

ISP

Immature single positive

LN

Lymph node

LTi

Lymphoid tissue inducer

NOD

Nonobese diabetic

NOG

NOD/Shi-scid/γcnull

NSG

NOD.Cg-Prkdcscid IL2rg tmlWjl /Sz

SCID

Severe combined immuno-deficiency

TFH

T follicular helper

UCB

Umbilical cord blood

Notes

Acknowledgments

We thank Dr. Mireille Centlivre for valuable suggestions and critical reading of the manuscript.

References

  1. 1.
    McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL. The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science. 1988;241(4873):1632–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Kamel-Reid S, Dick JE. Engraftment of immune-deficient mice with human hematopoietic stem cells. Science. 1988;242(4886):1706–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Mosier DE, Gulizia RJ, Baird SM, Wilson DB. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature. 1988;335(6187):256–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Legrand N, Weijer K, Spits H. Experimental models to study development and function of the human immune system in vivo. J Immunol. 2006;176(4):2053–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Legrand N, Ploss A, Balling R, Becker PD, Borsotti C, Brezillon N, et al. Humanized mice for modeling human infectious disease: challenges, progress, and outlook. Cell Host Microbe. 2009;6(1):5–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Manz MG. Human-hemato-lymphoid-system mice: opportunities and challenges. Immunity. 2007;26(5):537–41.PubMedCrossRefGoogle Scholar
  7. 7.
    Manz MG, Di Santo JP. Renaissance for mouse models of human hematopoiesis and immunobiology. Nat Immunol. 2009;10(10):1039–42.PubMedCrossRefGoogle Scholar
  8. 8.
    Shultz LD, Brehm MA, Garcia-Martinez JV, Greiner DL. Humanized mice for immune system investigation: progress, promise and challenges. Nature reviews Immunology. 2012;12(11):786–98. (Epub 2012/10/13).PubMedCentralPubMedGoogle Scholar
  9. 9.
    Ito R, Takahashi T, Katano I, Ito M. Current advances in humanized mouse models. Cell Mol Immunol. 2012;9(3):208–14. (Epub 2012/02/14).PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Rongvaux A, Takizawa H, Strowig T, Willinger T, Eynon EE, Flavell RA, et al. Human hemato-lymphoid system mice: current use and future potential for medicine. Annu Rev Immunol. 2013;31:635–74. (Epub 2013/01/22).PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Hiramatsu H, Nishikomori R, Heike T, Ito M, Kobayashi K, Katamura K, et al. Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/gammacnull mice model. Blood. 2003;102(3):873–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, et al. NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 2002;100(9):3175–82.PubMedCrossRefGoogle Scholar
  13. 13.
    Yahata T, Ando K, Nakamura Y, Ueyama Y, Shimamura K, Tamaoki N, et al. Functional human T lymphocyte development from cord blood CD34+ cells in nonobese diabetic/Shi-scid, IL-2 receptor gamma null mice. J Immunol. 2002;169(1):204–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S, et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol. 2005;174(10):6477–89.PubMedCrossRefGoogle Scholar
  15. 15.
    Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G, et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chainnull mice. Blood. 2005;106(5):1565–73.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Notta F, Doulatov S, Dick JE. Engraftment of human hematopoietic stem cells is more efficient in female NOD/SCID/IL-2Rgc-null recipients. Blood. 2010;115(18):3704–7. (Epub 2010/03/09).PubMedCrossRefGoogle Scholar
  17. 17.
    Majeti R, Park CY, Weissman IL. Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood. Cell Stem Cell. 2007;1(6):635–45.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB, Tennent B, et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol. 1995;154(1):180–91.PubMedGoogle Scholar
  19. 19.
    Takenaka K, Prasolava TK, Wang JC, Mortin-Toth SM, Khalouei S, Gan OI, et al. Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat Immunol. 2007;8(12):1313–23.PubMedCrossRefGoogle Scholar
  20. 20.
    Ito R, Katano I, Ida-Tanaka M, Kamisako T, Kawai K, Suemizu H, et al. Efficient xenoengraftment in severe immunodeficient NOD/Shi-scid IL2rgammanull mice is attributed to a lack of CD11c+B220+CD122+ cells. J Immunol. 2012;189(9):4313–20. (Epub 2012/09/29).PubMedCrossRefGoogle Scholar
  21. 21.
    Strowig T, Rongvaux A, Rathinam C, Takizawa H, Borsotti C, Philbrick W, et al. Transgenic expression of human signal regulatory protein alpha in Rag2−/−gamma(c)−/− mice improves engraftment of human hematopoietic cells in humanized mice. Proc Natl Acad Sci U S A. 2011;108(32):13218–23. (Epub 2011/07/27).PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Gimeno R, Weijer K, Voordouw A, Uittenbogaart CH, Legrand N, Alves NL, et al. Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2−/− gammac−/− mice: functional inactivation of p53 in developing T cells. Blood. 2004;104(13):3886–93.PubMedCrossRefGoogle Scholar
  23. 23.
    Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti JC, Lanzavecchia A, et al. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science. 2004;304(5667):104–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Legrand N, Huntington ND, Nagasawa M, Bakker AQ, Schotte R, Strick-Marchand H, et al. Functional CD47/signal regulatory protein alpha (SIRP(alpha)) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo. Proc Natl Acad Sci U S A. 2011;108(32):13224–9. (Epub 2011/07/27).PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Mazurier F, Fontanellas A, Salesse S, Taine L, Landriau S, Moreau-Gaudry F, et al. A novel immunodeficient mouse model–RAG2 x common cytokine receptor gamma chain double mutants—requiring exogenous cytokine administration for human hematopoietic stem cell engraftment. J Interferon Cytokine Res. 1999;19(5):533–41.PubMedCrossRefGoogle Scholar
  26. 26.
    Bosma GC, Custer RP, Bosma MJ. A severe combined immunodeficiency mutation in the mouse. Nature. 1983;301(5900):527–30.PubMedCrossRefGoogle Scholar
  27. 27.
    Bosma GC, Fried M, Custer RP, Carroll A, Gibson DM, Bosma MJ. Evidence of functional lymphocytes in some (leaky) scid mice. J Exp Med. 1988;167(3):1016–33.PubMedCrossRefGoogle Scholar
  28. 28.
    Bosma MJ. B and T cell leakiness in the scid mouse mutant. Immunodefic Rev. 1992;3(4):261–76. (Epub 1992/01/01).PubMedGoogle Scholar
  29. 29.
    Krowka JF, Sarin S, Namikawa R, McCune JM, Kaneshima H. Human T cells in the SCID-hu mouse are phenotypically normal and functionally competent. J Immunol. 1991;146(11):3751–6.PubMedGoogle Scholar
  30. 30.
    Melkus MW, Estes JD, Padgett-Thomas A, Gatlin J, Denton PW, Othieno FA, et al. Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1. Nat Med. 2006;12(11):1316–22.PubMedCrossRefGoogle Scholar
  31. 31.
    Brainard DM, Seung E, Frahm N, Cariappa A, Bailey CC, Hart WK, et al. Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice. J Virol. 2009;83(14):7305–21.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Lan P, Tonomura N, Shimizu A, Wang S, Yang YG. Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation. Blood. 2006;108(2):487–92.PubMedCrossRefGoogle Scholar
  33. 33.
    Denton PW, Garcia JV. Mucosal HIV-1 transmission and prevention strategies in BLT humanized mice. Trends Microbiol. 2012;20(6):268–74. (Epub 2012/04/17).PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Greenblatt MB, Vbranac V, Tivey T, Tsang K, Tager AM, Aliprantis AO. Graft versus host disease in the bone marrow, liver and thymus humanized mouse model. PloS One. 2012;7(9):e44664. (Epub 2012/09/08).PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Covassin L, Jangalwe S, Jouvet N, Laning J, Burzenski L, Shultz LD, et al. Human immune system development and survival of NOD-scid IL2rgamma (NSG) mice engrafted with human thymus and autologous hematopoietic stem cells. Clin Exp Immunol. 2013. (Epub 2013/07/23).Google Scholar
  36. 36.
    Lockridge JL, Zhou Y, Becker YA, Ma S, Kenney SC, Hematti P, et al. Mice engrafted with human fetal thymic tissue and hematopoietic stem cells develop pathology resembling chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2013;19(9):1310–22. (Epub 2013/06/29).Google Scholar
  37. 37.
    Scheeren FA, Nagasawa M, Weijer K, Cupedo T, Kirberg J, Legrand N, et al. T cell-independent development and induction of somatic hypermutation in human IgM+IgD+CD27+ B cells. J Exp Med. 2008;205(9):2033–42.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Dik WA, Pike-Overzet K, Weerkamp F, de Ridder D, de Haas EF, Baert MR, et al. New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling. J Exp Med. 2005;201(11):1715–23.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Res P, Martinez-Caceres E, Cristina Jaleco A, Staal F, Noteboom E, Weijer K, et al. CD34+CD38dim cells in the human thymus can differentiate into T, natural killer, and dendritic cells but are distinct from pluripotent stem cells. Blood. 1996;87(12):5196–206.PubMedGoogle Scholar
  40. 40.
    Blom B, Spits H. Development of human lymphoid cells. Annu Rev Immunol. 2006;24:287–320.PubMedCrossRefGoogle Scholar
  41. 41.
    Blom B, Verschuren MC, Heemskerk MH, Bakker AQ, van Gastel-Mol EJ, Wolvers-Tettero IL, et al. TCR gene rearrangements and expression of the pre-T cell receptor complex during human T-cell differentiation. Blood. 1999;93(9):3033–43.PubMedGoogle Scholar
  42. 42.
    Haddad R, Guardiola P, Izac B, Thibault C, Radich J, Delezoide AL, et al. Molecular characterization of early human T/NK and B-lymphoid progenitor cells in umbilical cord blood. Blood. 2004;104(13):3918–26.PubMedCrossRefGoogle Scholar
  43. 43.
    Hao QL, Zhu J, Price MA, Payne KJ, Barsky LW, Crooks GM. Identification of a novel, human multilymphoid progenitor in cord blood. Blood. 2001;97(12):3683–90. (Epub 2001/06/05).PubMedCrossRefGoogle Scholar
  44. 44.
    Haddad R, Guimiot F, Six E, Jourquin F, Setterblad N, Kahn E, et al. Dynamics of thymus-colonizing cells during human development. Immunity. 2006;24(2):217–30.PubMedCrossRefGoogle Scholar
  45. 45.
    Lepus CM, Gibson TF, Gerber SA, Kawikova I, Szczepanik M, Hossain J, et al. Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/gammac−/−, Balb/c-Rag1−/−gammac−/−, and C.B-17-scid/bg immunodeficient mice. Hum Immunol. 2009;70(10):790–802.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Lang J, Kelly M, Freed BM, McCarter MD, Kedl RM, Torres RM, et al. Studies of lymphocyte reconstitution in a humanized mouse model reveal a requirement of T cells for human B cell maturation. J Immunol. 2013;190(5):2090–101. (Epub 2013/01/22).PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    van Lent AU, Dontje W, Nagasawa M, Siamari R, Bakker AQ, Pouw SM, et al. IL-7enhances thymic human T cell development in “human immune system” Rag2−/−IL-2Rgammac−/− mice without affecting peripheral T cell homeostasis. J Immunol. 2009;183(12):7645–55.PubMedCrossRefGoogle Scholar
  48. 48.
    Denton PW, Nochi T, Lim A, Krisko JF, Martinez-Torres F, Choudhary SK, et al. IL-2 receptor gamma-chain molecule is critical for intestinal T-cell reconstitution in humanized mice. Mucosal Immunol. 2012;5(5):555–66. (Epub 2012/05/10).PubMedCentralPubMedGoogle Scholar
  49. 49.
    Sun Z, Denton PW, Estes JD, Othieno FA, Wei BL, Wege AK, et al. Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1. J Exp Med. 2007;204(4):705–14.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Joo SY, Chung YS, Choi B, Kim M, Kim JH, Jun TG, et al. Systemic human T cell developmental processes in humanized mice cotransplanted with human fetal thymus/liver tissue and hematopoietic stem cells. Transplantation. 2012;94(11):1095–102. (Epub 2012/12/12).PubMedCrossRefGoogle Scholar
  51. 51.
    Huntington ND, Alves NL, Legrand N, Lim A, Strick-Marchand H, Plet A, et al. Autonomous and extrinsic regulation of thymopoiesis inhuman immune system (HIS) mice. Eur J Immunol. 2011;41(10):2883–93. (Epub 2011/07/09).PubMedCrossRefGoogle Scholar
  52. 52.
    Spits H. Development of alphabeta T cells in the human thymus. Nat Rev Immunol. 2002;2(10):760–72.PubMedCrossRefGoogle Scholar
  53. 53.
    Pek EA, Chan T, Reid S, Ashkar AA. Characterization and IL-15 dependence of NK cells in humanized mice. Immunobiology. 2011;216(1–2):218–24. (Epub 2010/07/16).PubMedCrossRefGoogle Scholar
  54. 54.
    Huntington ND, Legrand N, Alves NL, Jaron B, Weijer K, Plet A, et al. IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J Exp Med. 2009;206:25–34.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Legrand N, Cupedo T, van Lent AU, Ebeli MJ, Weijer K, Hanke T, et al. Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in “human immune system” Rag2(−/−)gammac(−/−) mice. Blood. 2006;108(1):238–45.PubMedCrossRefGoogle Scholar
  56. 56.
    Onoe T, Kalscheuer H, Danzl N, Chittenden M, Zhao G, Yang YG, et al. Human natural regulatory T cell development, suppressive function, and postthymic maturation in a humanized mouse model. J Immunol. 2011;187(7):3895–903. (Epub 2011/08/31).PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Kalscheuer H, Danzl N, Onoe T, Faust T, Winchester R, Goland R, et al. A model for personalized in vivo analysis of human immune responsiveness. Sci Transl Med. 2012;4(125):125ra30. (Epub 2012/03/17).PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Billerbeck E, Barry WT, Mu K, Dorner M, Rice CM, Ploss A. Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2Rgamma(null) humanized mice. Blood. 2011;117(11):3076–86. (Epub 2011/01/22).PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Jiang Q, Zhang L, Wang R, Jeffrey J, Washburn ML, Brouwer D, et al. FoxP3+CD4+ regulatory T cells play an important role in acute HIV-1 infection in humanized Rag2−/−gammaC−/− mice in vivo. Blood. 2008;112(7):2858–68.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Becker PD, Legrand N, van Geelen CM, Noerder M, Huntington ND, Lim A, et al. Generation of human antigen-specific monoclonal IgM antibodies using vaccinated “human immune system” mice. PloS one. 2010;5(10).Google Scholar
  61. 61.
    Vuyyuru R, Patton J, Manser T. Human immune system mice: current potential and limitations for translational research on human antibody responses. Immunol Res. 2011;51(2–3):257–66. (Epub 2011/11/01).PubMedCrossRefGoogle Scholar
  62. 62.
    Parel Y, Chizzolini C. CD4+ CD8+ double positive (DP) T cells in health and disease. Autoimmun Rev. 2004;3(3):215–20.PubMedCrossRefGoogle Scholar
  63. 63.
    Rozemuller H, Knaan-Shanzer S, Hagenbeek A, van Bloois L, Storm G, Martens AC. Enhanced engraftment of human cells in RAG2/gammac double-knockout mice after treatment with CL2MDP liposomes. Exp Hematol. 2004;32(11):1118–25.PubMedCrossRefGoogle Scholar
  64. 64.
    Brown EJ, Frazier WA. Integrin-associated protein (CD47) and its ligands. Trends Cell Biol. 2001;11(3):130–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Sarfati M, Fortin G, Raymond M, Susin S. CD47 in the immune response: role of thrombospondin and SIRP-alpha reverse signaling. Curr Drug Targets. 2008;9(10):842–50.PubMedCrossRefGoogle Scholar
  66. 66.
    Yamauchi T, Takenaka K, Urata S, Shima T, Kikushige Y, Tokuyama T, et al. Polymorphic Sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment. Blood. 2013;121(8):1316–25. (Epub 2013/01/08).PubMedCrossRefGoogle Scholar
  67. 67.
    Berzins SP, Godfrey DI, Miller JF, Boyd RL. A central role for thymic emigrants in peripheral T cell homeostasis. Proc Natl Acad Sci U S A. 1999;96(17):9787–91.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Gabor MJ, Scollay R, Godfrey DI. Thymic T cell export is not influenced by the peripheral T cell pool. Eur J Immunol. 1997;27(11):2986–93. (Epub 1997/12/12).PubMedCrossRefGoogle Scholar
  69. 69.
    Scollay RG, Butcher EC, Weissman IL. Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur J Immunol. 1980;10(3):210–8. (Epub 1980/03/01).PubMedCrossRefGoogle Scholar
  70. 70.
    Almeida AR, Borghans JA, Freitas AA. T cell homeostasis: thymus regeneration and peripheral T cell restoration in mice with a reduced fraction of competent precursors. J Exp Med. 2001;194(5):591–9.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Alves NL, Huntington ND, Mention JJ, Richard-Le Goff O, Di Santo JP. Cutting edge: a thymocyte-thymic epithelial cell cross-talk dynamically regulates intrathymic IL-7 expression in vivo. J Immunol. 2010;184(11):5949–53.PubMedCrossRefGoogle Scholar
  72. 72.
    Mazzucchelli R, Durum SK. Interleukin-7 receptor expression: intelligent design. Nat Rev Immunology. 2007;7(2):144–54.CrossRefGoogle Scholar
  73. 73.
    Huang HY, Luther SA. Expression and function of interleukin-7 in secondary and tertiary lymphoid organs. Semin Immunol. 2012;24(3):175–89. (Epub 2012/03/27).PubMedCrossRefGoogle Scholar
  74. 74.
    O’Connell RM, Balazs AB, Rao DS, Kivork C, Yang L, Baltimore D. Lentiviral vector delivery of human interleukin-7 (hIL-7) to human immune system (HIS) mice expands T lymphocyte populations. PloS One. 2010;5(8):e12009.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Cupedo T, Mebius RE. Cellular interactions in lymph node development. J Immunol. 2005;174(1):21–5.PubMedCrossRefGoogle Scholar
  76. 76.
    Murooka TT, Deruaz M, Marangoni F, Vrbanac VD, Seung E, von Andrian UH, et al. HIV-infected T cells are migratory vehicles for viral dissemination. Nature. 2012;490(7419):283–7. (Epub 2012/08/03).PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Bromley SK, Mempel TR, Luster AD. Orchestrating the orchestrators: chemokines in control of T cell traffic. Nat Immunol. 2008;9(9):970–80. (Epub 2008/08/20).PubMedCrossRefGoogle Scholar
  78. 78.
    Bernink JH, Peters CP, Munneke M, Te Velde AA, Meijer SL, Weijer K, et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol. 2013;14(3):221–9. (Epub 2013/01/22).PubMedCrossRefGoogle Scholar
  79. 79.
    Pham HP, Manuel M, Petit N, Klatzmann D, Cohen-Kaminsky S, Six A, et al. Half of the T-cell repertoire combinatorial diversity is genetically determined in humans and humanized mice. Eur J Immunol. 2012;42(3):760–70. (Epub 2011/11/23).PubMedCrossRefGoogle Scholar
  80. 80.
    Huntington ND, Alves NL, Legrand N, Lim A, Strick-Marchand H, Mention JJ, et al. IL-15 transpresentation promotes both human T-cell reconstitution and T-cell-dependent antibody responses in vivo. Proc Natl Acad Sci U S A. 2011;108(15):6217–22. (Epub 2011/03/30).PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Marodon G, Desjardins D, Mercey L, Baillou C, Parent P, Manuel M, et al. High diversity of the immune repertoire in humanized NOD.SCID.gamma c−/− mice. Eur J Immunol. 2009;39(8):2136–45. (Epub 2009/07/03).PubMedCrossRefGoogle Scholar
  82. 82.
    Zinkernagel RM, Althage A. On the role of thymic epithelium vs. bone marrow-derived cells in repertoire selection of T cells. Proc Natl Acad Sci U S A. 1999;96(14):8092–7.PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Sato Y, Nagata S, Takiguchi M. Effective elicitation of human effector CD8(+) T cells in HLA-B*51:01 transgenic humanized mice after infection with HIV-1. PloS One. 2012;7(8):e42776. (Epub 2012/08/11).PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Strowig T, Gurer C, Ploss A, Liu YF, Arrey F, Sashihara J, et al. Priming of protective T cell responses against virus-induced tumors in mice with human immune system components. J Exp Med. 2009;206(6):1423–34.PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Shultz LD, Saito Y, Najima Y, Tanaka S, Ochi T, Tomizawa M, et al. Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2r gamma(null) humanized mice. Proc Natl Acad Sci U S A. 2010;107(29):13022–7.PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    Jaiswal S, Pearson T, Friberg H, Shultz LD, Greiner DL, Rothman AL, et al. Dengue virus infection and virus-specific HLA-A2 restricted immune responses in humanized NOD-scid IL2rgammanull mice. PloS One. 2009;4(10):e7251. (Epub 2009/10/06).PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Jung KC, Park CG, Jeon YK, Park HJ, Ban YL, Min HS, et al. In situ induction of dendritic cell-based T cell tolerance in humanized mice and nonhuman primates. J Exp Med. 2011;208(12):2477–88. (Epub 2011/10/26).Google Scholar
  88. 88.
    Watanabe N, Wang YH, Lee HK, Ito T, Cao W, Liu YJ. Hassall’s corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature. 2005;436(7054):1181–5.PubMedCrossRefGoogle Scholar
  89. 89.
    Rajesh D, Zhou Y, Jankowska-Gan E, Roenneburg DA, Dart ML, Torrealba J, et al. Th1 and Th17 immunocompetence in humanized NOD/SCID/IL2rgammanull mice. Hum Immunol. 2010;71(6):551–9. (Epub 2010/03/20).PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    King C. New insights into the differentiation and function of T follicular helper cells. Nature reviews Immunology. 2009;9(11):757–66.PubMedGoogle Scholar
  91. 91.
    Rodriguez-Bayona B, Ramos-Amaya A, Bernal J, Campos-Caro A, Brieva JA. Cutting edge: IL-21 derived from human follicular helper T cells acts as a survival factor for secondary lymphoid organ, but not for bone marrow, plasma cells. J Immunol. 2012;188(4):1578–81. (Epub 2012/01/18).PubMedCrossRefGoogle Scholar
  92. 92.
    Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. J Immunol. 2004;172(5):2731–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Di Santo JP Mention JJ. Dendritic cell-boosted humanized immune system mice. PCT/US2010/029800. WO 2010/115115 A1. Patent. 2010.Google Scholar
  94. 94.
    Bjorkstrom NK, Riese P, Heuts F, Andersson S, Fauriat C, Ivarsson MA, et al. Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education. Blood. 2010;116(19):3853–64.PubMedCrossRefGoogle Scholar
  95. 95.
    Wils EJ, Rombouts EJ, van Mourik I, Spits H, Legrand N, Braakman E, et al. Stem cell factor consistently improves thymopoiesis after experimental transplantation of murine or human hematopoietic stem cells in immunodeficient mice. J Immunol. 2011;187(6):2974–81. (Epub 2011/08/24).PubMedCrossRefGoogle Scholar
  96. 96.
    Takagi S, Saito Y, Hijikata A, Tanaka S, Watanabe T, Hasegawa T, et al. Membrane-bound human SCF/KL promotes in vivo human hematopoietic engraftment and myeloid differentiation. Blood. 2012;119(12):2768–77. (Epub 2012/01/27).PubMedCentralPubMedCrossRefGoogle Scholar
  97. 97.
    Willinger T, Rongvaux A, Strowig T, Manz MG, Flavell RA. Improving human hemato-lymphoid-system mice by cytokine knock-in gene replacement. Trends Immunol. 2011;32(7):321–7. (Epub 2011/06/24).PubMedCrossRefGoogle Scholar
  98. 98.
    Willinger T, Rongvaux A, Takizawa H, Yancopoulos GD, Valenzuela DM, Murphy AJ, et al. Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung. Proc Natl Acad Sci U S A. 2011;108(6):2390–5. (Epub 2011/01/26).PubMedCentralPubMedCrossRefGoogle Scholar
  99. 99.
    Rongvaux A, Willinger T, Takizawa H, Rathinam C, Auerbach W, Murphy AJ, et al. Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo. Proc Natl Acad Sci U S A. 2011;108(6):2378–83. (Epub 2011/01/26).PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Chen Q, Khoury M, Chen J. Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice. Proc Natl Acad Sci U S A. 2009;106(51):21783–8.PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    De Giovanni C, Nicoletti G, Landuzzi L, Romani F, Croci S, Palladini A, et al. Human responses against HER-2-positive cancer cells in human immune system-engrafted mice. Br J Cancer. 2012;107(8):1302–09. (Epub 2012/08/30).Google Scholar
  102. 102.
    Chen Q, He F, Kwang J, Chan JK, Chen J. GM-CSF and IL-4 stimulate antibody responses in humanized mice by promoting T, B, and dendritic cell maturation. J Immunol. 2012;189(11):5223–9. (Epub 2012/10/24).PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Vinuesa CG, Linterman MA, Goodnow CC, Randall KL. T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol Rev. 2010;237(1):72–89.PubMedCrossRefGoogle Scholar
  104. 104.
    Cyster JG. B cell follicles and antigen encounters of the third kind. Nat Immunol. 2010;11(11):989–96. (Epub 2010/10/21).PubMedCrossRefGoogle Scholar
  105. 105.
    Krautler NJ, Kana V, Kranich J, Tian Y, Perera D, Lemm D, et al. Follicular dendritic cells emerge from ubiquitous perivascular precursors. Cell. 2012;150(1):194–206. (Epub 2012/07/10).PubMedCentralPubMedCrossRefGoogle Scholar
  106. 106.
    Zeng M, Paiardini M, Engram JC, Beilman GJ, Chipman JG, Schacker TW, et al. Critical role for CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution. Blood. 2012;120:1856–67. (Epub 2012/05/23).PubMedCentralPubMedCrossRefGoogle Scholar
  107. 107.
    Ame-Thomas P, Maby-El Hajjami H, Monvoisin C, Jean R, Monnier D, Caulet-Maugendre S, et al. Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis. Blood. 2007;109(2):693–702. (Epub 2006/09/21).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.AXENISParisFrance
  2. 2.Tytgat Institute for Liver and Intestinal Research, AMC-UvAAmsterdamThe Netherlands

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